Cognitive deficits persist in the combination antiretroviral era: Preliminary results from the Co-morBidity in Relation to AIDS (COBRA) collaboration London cohort

Abstract

Background: HIV is a neurotropic virus that if left untreated leads to a frank dementia in a significant proportion of patients. Modern combination antiretroviral therapy (cART) has transformed HIV into a chronic disease with life expectancy approaching normal. The more severe forms of HIV associated neurocognitive dysfunction (HAND) are now rarely seen but there have been many reports of more subtle cognitive deficits occurring in up to 50% of patients in the modern era. Unfortunately many previous studies have had heterogeneous patient groups or lacked appropriate controls making extrapolation to well treated patients, common in current practice, difficult. This study set out to investigate the true prevalence of cognitive dysfunction and the mechanisms underlying it in an older group of HIV positive individuals on effect cART. Methods: To date 46 participants (33 HIV-positive patients and 13 HIV-negative controls) have been recruited into the London cohort of the COBRA observational study. All participants were aged over 50 (mean age 61 ± 7.7 years) and were predominantly male (87%). All HIV positive patients were on fully suppressive stable cART > 12 months. The two groups were well matched in terms of age, gender, sexual orientation, ethnicity and educational attainment. Subjects underwent a full cognitive battery in addition to MRI scanning with a 64-direction diffusion protocol. Mean FA (fractional anisotropy) for the major white matter tracts was calculated using a white matter skeleton created from the centre of tracts common to the group and standard atlases. Results: Poorer performance on trail making tests A and B (p = 0.007 and < 0.001 respectively), the Stroop test (p = 0.006), grooved peg board test (p = 0.004) and the Wisconsin card sort test (p = 0.002) were observed in the HIV-positive group compared to the control group. After adjusting for age the mean white matter skeleton FA was highly significantly correlated (p < 0.01) with all the abnormal cognitive tests. Significantly lower FA values were observed in 24% of the major white matter tracts of the HIV-positive group compared to controls. Conclusions: Cognitive deficits in a variety of domains persist despite full suppression of HIV replication (at least in the plasma compartment) when compared to well matched controls. The reduction in cognitive performance observed is mediated in part by decreased white matter integrity manifested as lower FA values in numerous major white matter tracts. Further analysis of other MRI modalities and lumbar puncture findings of the same cohort are awaited and these may shed light further on the pathophysiology of HAND in those on fully suppressive therapy.